The synthetic route of 33406-96-1 has been constantly updated, and we look forward to future research findings.
Application of 33406-96-1, These common heterocyclic compound, 33406-96-1, name is 1-Chloro-4-fluoro-2-methylbenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a solution of 2-chloro-5-fluorotoluene (5.0 g) in acetic anhydride (40 ml) was added dropwise under ice-cooling concentrated sulfuric acid (40 ml), and then added dropwise a solution of anhydrous chromic acid (9.3 g) in acetic anhydride (40 ml) for 2 hours. The mixture was stirred at the same temperature for 1 hour, poured into ice-water and extracted with diethylether. The organic layer was washed with sodium carbonate solution, water and saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in tetrahydrofuran (10 ml). To the mixture were added water (4 ml) and concentrated sulfuric acid (4 ml), and the mixture was stirred at 100 C. for 30 minutes and cooled. The reaction solution was extracted with ethyl acetate. The organic layer was washed with sodium carbonate solution, water and saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated to give the residue, which was subjected to silica gel column chromatography to give 2-chloro-5-fluorobenzaldehyde (1.6 g). The similar reaction was repeated to give 2-chloro-5-fluorobenzaldehyde (1.2 g). In water (55 ml) was dissolved sodium hydroxide (0.78 g), and to the mixture was added acetone (55 ml), and then added dropwise a solution of 2-chloro-5-fluorobenzaldehyde (2.8 g) in acetone (10 ml). The reaction solution was stirred at room temperature for 2 hours, and acetone was evaporated under reduced pressure. The residue was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(2-chloro-5-fluorophenyl)-3-buten-2-one (0.24 g). To a solution of 20% sodium ethoxide in ethanol (0.43 g) was added at room temperature diethyl malonate (0.2 g), and then added little by little 4-(2-chloro-5-fluorophenyl)-3-buten-2-one (0.24 g). The mixture was stirred at room temperature for 30 minutes, refluxed for 2 hours and cooled, and the solvent was evaporated. The residue was dissolved in water, and the aqueous layer was washed with ethyl acetate and concentrated. To the reside was added 2M sodium hydroxide (0.7 ml), and the mixture was refluxed for 2 hours cooled. To the mixture was added 2.5M sulfuric acid (0.7 ml), and the mixture was refluxed for 15 minutes. The mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated to give 5-(2-chloro-5-fluorophenyl)cyclohexane-1,3-dione (0.17 g) as oil. A solution of 5-(5-chloro-2-fluorophenyl)cyclohexane-1,3-dione (0.17 g) and ammonium acetate (0.16 g) in ethanol (10 ml) was refluxed for 12 hours. Under reduced pressure, the solvent was evaporated, and to the residue was added ethyl acetate. The organic layer was washed with sodium carbonate solution, water and saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in ethanol (3.5 ml) and toluene (6 ml). To the mixture were added 3-oxobutylaldehydedimethylacetal (0.21 g) and powdery potassium hydroxide (34 mg), and the mixture was refluxed. To the mixture was added powdery potassium hydroxide (0.07 g) 30 minutes later; powdery potassium hydroxide (0.07 g) and 3-oxobutylaldehydedimethylacetal (17 mg) 1 hour later; and powdery potassium hydroxide (0.07 g) 1.5 hours later. Then, the mixture was stirred at the same temperature for 2 hours and cooled. Under reduced pressure, the solvent was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate. Under reduced pressure, ethyl acetate was evaporated, and the residue was subjected to silica gel column chromatography(ethyl acetate-hexane) to give 7-(2-chloro-5-fluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one. To a solution of 7-(2-chloro-5-fluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one in ethanol (10 ml) were added aminoguanidine hydrochloride (0.041 g), concentrated hydrochloric acid (0.078 ml) and water (0.078 ml), and the mixture was refluxed for 4 hours. Under reduced pressure, the solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate, and to the aqueous layer was added sodium hydrogen carbonate solution to make it alkaline. The solution was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried with magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in 1N hydrochloric acid (1 ml) and concentrated to give crystals, which were recrystallized from ethanol-ethyl acetate to give 7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline hydrochloride (Compound 170) (0.05 g) as colorless crystals. mp. 268 C. (decomp.). 1H-NMR(DMSO-d6) delta: 2.76-3.05 (1H, m), …
The synthetic route of 33406-96-1 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Takeda Chemical Industries, Ltd.; US6350749; (2002); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics